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The intracellular sensor NLRP3 mediates key innate and healing responses to influenza A virus via the regulation of caspase-1.

Authors: Thomas, PG  Dash, P  Aldridge JR, JR  Ellebedy, AH  Reynolds, C  Funk, AJ  Martin, WJ  Lamkanfi, M  Webby, RJ  Boyd, KL  Doherty, PC  Kanneganti, TD 
Citation: Thomas PG, etal., Immunity. 2009 Apr 17;30(4):566-75. Epub 2009 Apr 9.
Pubmed: (View Article at PubMed) PMID:19362023
DOI: Full-text: DOI:10.1016/j.immuni.2009.02.006

Virus-induced interlukin-1beta (IL-1beta) and IL-18 production in macrophages are mediated via caspase-1 pathway. Multiple microbial components, including viral RNA, are thought to trigger assembly of the cryopyrin inflammasome resulting in caspase-1 activation. Here, we demonstrated that Nlrp3(-/-) and Casp1(-/-) mice were more susceptible than wild-type mice after infection with a pathogenic influenza A virus. This enhanced morbidity correlated with decreased neutrophil and monocyte recruitment and reduced cytokine and chemokine production. Despite the effect on innate immunity, cryopyrin-deficiency was not associated with any obvious defect in virus control or on the later emergence of the adaptive response. Early epithelial necrosis was, however, more severe in the infected mutants, with extensive collagen deposition leading to later respiratory compromise. These findings reveal a function of the cryopyrin inflammasome in healing responses. Thus, cryopyrin and caspase-1 are central to both innate immunity and to moderating lung pathology in influenza pneumonia.


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RGD Object Information
RGD ID: 5130181
Created: 2011-04-07
Species: All species
Last Modified: 2011-04-07
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.